Incidental Mutation 'R5007:Pcdh18'
| ID |
390193 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Pcdh18
|
| Ensembl Gene |
ENSMUSG00000037892 |
| Gene Name |
protocadherin 18 |
| Synonyms |
PCDH68L |
| MMRRC Submission |
042598-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R5007 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
3 |
| Chromosomal Location |
49697745-49711723 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 49708906 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Asparagine to Serine
at position 803
(N803S)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000141995
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000035931]
[ENSMUST00000191794]
|
| AlphaFold |
Q8VHR0 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000035931
AA Change: N803S
PolyPhen 2
Score 0.057 (Sensitivity: 0.94; Specificity: 0.84)
|
| SMART Domains |
Protein: ENSMUSP00000039245
Gene: ENSMUSG00000037892
AA Change: N803S
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
12 |
21 |
N/A |
INTRINSIC |
|
CA
|
51 |
135 |
1.36e-1 |
SMART |
|
CA
|
159 |
244 |
3.78e-20 |
SMART |
|
CA
|
268 |
352 |
1.12e-22 |
SMART |
|
CA
|
382 |
463 |
5.76e-25 |
SMART |
|
CA
|
487 |
574 |
2.51e-25 |
SMART |
|
CA
|
603 |
684 |
8e-3 |
SMART |
|
transmembrane domain
|
698 |
720 |
N/A |
INTRINSIC |
|
low complexity region
|
772 |
783 |
N/A |
INTRINSIC |
|
low complexity region
|
988 |
1009 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000191794
AA Change: N803S
PolyPhen 2
Score 0.230 (Sensitivity: 0.91; Specificity: 0.88)
|
| SMART Domains |
Protein: ENSMUSP00000141995
Gene: ENSMUSG00000037892
AA Change: N803S
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
27 |
N/A |
INTRINSIC |
|
CA
|
51 |
135 |
6.6e-4 |
SMART |
|
CA
|
159 |
244 |
1.9e-22 |
SMART |
|
CA
|
268 |
352 |
5.6e-25 |
SMART |
|
CA
|
382 |
463 |
2.7e-27 |
SMART |
|
CA
|
487 |
574 |
1.2e-27 |
SMART |
|
CA
|
603 |
684 |
3.9e-5 |
SMART |
|
transmembrane domain
|
698 |
720 |
N/A |
INTRINSIC |
|
low complexity region
|
772 |
783 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000193600
|
| Predicted Effect |
unknown
Transcript: ENSMUST00000194603
AA Change: N336S
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000195086
|
| Meta Mutation Damage Score |
0.0609 |
| Coding Region Coverage |
- 1x: 99.0%
- 3x: 98.1%
- 10x: 95.6%
- 20x: 89.6%
|
| Validation Efficiency |
99% (89/90) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. This gene encodes a protein which contains 6 extracellular cadherin domains, a transmembrane domain and a cytoplasmic tail differing from those of the classical cadherins. Although its specific function is undetermined, the cadherin-related neuronal receptor is thought to play a role in the establishment and function of specific cell-cell connections in the brain. [provided by RefSeq, Jul 2008]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 76 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 2310022A10Rik |
C |
G |
7: 27,278,192 (GRCm39) |
T242R |
probably damaging |
Het |
| Abca8b |
T |
C |
11: 109,827,590 (GRCm39) |
T1473A |
probably damaging |
Het |
| Adam22 |
T |
C |
5: 8,217,393 (GRCm39) |
Y134C |
probably damaging |
Het |
| Alg9 |
T |
A |
9: 50,699,524 (GRCm39) |
M183K |
probably damaging |
Het |
| Ambra1 |
T |
C |
2: 91,602,655 (GRCm39) |
I213T |
possibly damaging |
Het |
| Ankrd55 |
T |
A |
13: 112,504,466 (GRCm39) |
V376D |
probably benign |
Het |
| Ano4 |
A |
C |
10: 88,948,807 (GRCm39) |
V166G |
probably benign |
Het |
| Aox3 |
T |
A |
1: 58,202,583 (GRCm39) |
C730S |
probably benign |
Het |
| Apc |
T |
A |
18: 34,446,016 (GRCm39) |
Y953N |
probably damaging |
Het |
| Ass1 |
T |
C |
2: 31,391,544 (GRCm39) |
F273S |
possibly damaging |
Het |
| Atg2b |
T |
C |
12: 105,610,135 (GRCm39) |
|
probably null |
Het |
| B3gnt9 |
A |
G |
8: 105,981,122 (GRCm39) |
Y89H |
probably damaging |
Het |
| Cd38 |
T |
G |
5: 44,063,506 (GRCm39) |
F200V |
probably damaging |
Het |
| Cep170 |
G |
T |
1: 176,597,380 (GRCm39) |
R388S |
probably benign |
Het |
| Col22a1 |
A |
T |
15: 71,816,271 (GRCm39) |
D614E |
probably damaging |
Het |
| Crybg3 |
C |
A |
16: 59,378,463 (GRCm39) |
|
probably benign |
Het |
| Ctdp1 |
A |
T |
18: 80,463,695 (GRCm39) |
S114T |
probably damaging |
Het |
| Dctd |
C |
T |
8: 48,590,449 (GRCm39) |
|
probably benign |
Het |
| Dmtf1 |
T |
C |
5: 9,172,439 (GRCm39) |
|
probably benign |
Het |
| Dnhd1 |
G |
A |
7: 105,362,283 (GRCm39) |
V3715M |
probably damaging |
Het |
| Dok1 |
A |
T |
6: 83,009,297 (GRCm39) |
L185H |
probably damaging |
Het |
| Dpep1 |
T |
C |
8: 123,926,117 (GRCm39) |
V152A |
probably damaging |
Het |
| Eif2ak1 |
G |
T |
5: 143,810,698 (GRCm39) |
R136L |
probably benign |
Het |
| Eml5 |
A |
T |
12: 98,797,224 (GRCm39) |
S1063T |
probably damaging |
Het |
| Fam171b |
T |
A |
2: 83,685,853 (GRCm39) |
L179* |
probably null |
Het |
| Flot1 |
G |
T |
17: 36,135,267 (GRCm39) |
|
probably benign |
Het |
| Fmn2 |
A |
T |
1: 174,571,866 (GRCm39) |
H1491L |
probably damaging |
Het |
| Frem1 |
C |
T |
4: 82,859,049 (GRCm39) |
|
probably benign |
Het |
| Gdf2 |
A |
G |
14: 33,666,863 (GRCm39) |
D195G |
probably benign |
Het |
| Golga4 |
T |
G |
9: 118,387,368 (GRCm39) |
C1497G |
probably benign |
Het |
| Gpaa1 |
T |
A |
15: 76,215,868 (GRCm39) |
C33* |
probably null |
Het |
| Hectd1 |
A |
T |
12: 51,849,443 (GRCm39) |
C254S |
possibly damaging |
Het |
| Hspa1b |
C |
T |
17: 35,177,086 (GRCm39) |
A300T |
probably benign |
Het |
| Igf2bp2 |
A |
G |
16: 21,898,246 (GRCm39) |
I233T |
probably damaging |
Het |
| Iqce |
C |
A |
5: 140,661,003 (GRCm39) |
A491S |
possibly damaging |
Het |
| Irak3 |
A |
G |
10: 119,982,334 (GRCm39) |
|
probably null |
Het |
| Kcnip1 |
T |
A |
11: 33,592,495 (GRCm39) |
H124L |
probably benign |
Het |
| Klhdc10 |
G |
A |
6: 30,450,640 (GRCm39) |
R393Q |
probably benign |
Het |
| Klhl28 |
C |
T |
12: 65,004,001 (GRCm39) |
E171K |
probably damaging |
Het |
| Map2 |
T |
C |
1: 66,452,448 (GRCm39) |
V288A |
possibly damaging |
Het |
| Mdp1 |
C |
T |
14: 55,896,683 (GRCm39) |
R126Q |
probably damaging |
Het |
| Meltf |
A |
G |
16: 31,706,380 (GRCm39) |
D288G |
possibly damaging |
Het |
| Mgat4e |
T |
A |
1: 134,468,890 (GRCm39) |
I385F |
probably benign |
Het |
| Mical3 |
A |
C |
6: 121,015,030 (GRCm39) |
V211G |
probably damaging |
Het |
| Mlh1 |
A |
G |
9: 111,100,478 (GRCm39) |
*39R |
probably null |
Het |
| Mre11a |
A |
G |
9: 14,721,116 (GRCm39) |
D345G |
probably benign |
Het |
| Mroh2a |
GCCC |
GC |
1: 88,159,979 (GRCm39) |
|
probably null |
Het |
| Msh2 |
C |
A |
17: 88,030,841 (GRCm39) |
A906E |
probably benign |
Het |
| Nat1 |
T |
G |
8: 67,944,077 (GRCm39) |
L154R |
probably benign |
Het |
| Nlrp4a |
A |
G |
7: 26,161,905 (GRCm39) |
D851G |
probably damaging |
Het |
| Npas4 |
A |
C |
19: 5,039,684 (GRCm39) |
V54G |
possibly damaging |
Het |
| Or13n4 |
T |
C |
7: 106,423,364 (GRCm39) |
Y123C |
probably damaging |
Het |
| Pcbp4 |
G |
A |
9: 106,339,292 (GRCm39) |
G100R |
probably damaging |
Het |
| Pcdh17 |
A |
G |
14: 84,770,737 (GRCm39) |
T1072A |
probably benign |
Het |
| Ppat |
C |
T |
5: 77,076,525 (GRCm39) |
|
probably benign |
Het |
| Ppm1l |
T |
A |
3: 69,224,931 (GRCm39) |
L11Q |
probably damaging |
Het |
| Pram1 |
T |
A |
17: 33,864,411 (GRCm39) |
V658E |
probably damaging |
Het |
| Prr12 |
C |
T |
7: 44,699,225 (GRCm39) |
|
probably benign |
Het |
| Prxl2b |
A |
G |
4: 154,981,531 (GRCm39) |
|
probably null |
Het |
| Ptprq |
A |
G |
10: 107,444,137 (GRCm39) |
V1489A |
probably benign |
Het |
| Ryr1 |
T |
A |
7: 28,768,540 (GRCm39) |
I2817F |
probably damaging |
Het |
| Sall2 |
A |
G |
14: 52,551,950 (GRCm39) |
L413P |
probably damaging |
Het |
| Slc7a9 |
T |
A |
7: 35,153,554 (GRCm39) |
M185K |
probably benign |
Het |
| Stag2 |
C |
T |
X: 41,355,130 (GRCm39) |
H1149Y |
possibly damaging |
Het |
| Timm10b |
T |
A |
7: 105,290,298 (GRCm39) |
Y64N |
probably damaging |
Het |
| Tmem30c |
T |
C |
16: 57,086,868 (GRCm39) |
T312A |
probably benign |
Het |
| Tmem9b |
G |
T |
7: 109,344,550 (GRCm39) |
C17* |
probably null |
Het |
| Vmn2r68 |
C |
A |
7: 84,881,622 (GRCm39) |
R486L |
probably benign |
Het |
| Xkr9 |
T |
A |
1: 13,771,387 (GRCm39) |
I301N |
probably damaging |
Het |
| Xpo7 |
T |
C |
14: 70,925,704 (GRCm39) |
Q446R |
probably damaging |
Het |
| Ythdf3 |
T |
C |
3: 16,259,362 (GRCm39) |
V503A |
possibly damaging |
Het |
| Zfp280b |
T |
A |
10: 75,875,048 (GRCm39) |
V309D |
probably damaging |
Het |
| Zfp53 |
T |
A |
17: 21,729,772 (GRCm39) |
C602S |
probably benign |
Het |
| Zfp616 |
A |
T |
11: 73,974,643 (GRCm39) |
N395I |
possibly damaging |
Het |
| Zfp644 |
T |
C |
5: 106,783,867 (GRCm39) |
I862M |
probably benign |
Het |
| Zfp715 |
T |
C |
7: 42,949,019 (GRCm39) |
T314A |
possibly damaging |
Het |
|
| Other mutations in Pcdh18 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00543:Pcdh18
|
APN |
3 |
49,707,828 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL00639:Pcdh18
|
APN |
3 |
49,710,065 (GRCm39) |
missense |
probably benign |
0.34 |
|
IGL00954:Pcdh18
|
APN |
3 |
49,710,838 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01338:Pcdh18
|
APN |
3 |
49,710,590 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01339:Pcdh18
|
APN |
3 |
49,710,247 (GRCm39) |
missense |
probably benign |
0.35 |
|
IGL01687:Pcdh18
|
APN |
3 |
49,707,982 (GRCm39) |
splice site |
probably benign |
|
|
IGL01727:Pcdh18
|
APN |
3 |
49,710,149 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL01788:Pcdh18
|
APN |
3 |
49,710,371 (GRCm39) |
nonsense |
probably null |
|
|
IGL01824:Pcdh18
|
APN |
3 |
49,709,223 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01834:Pcdh18
|
APN |
3 |
49,711,279 (GRCm39) |
missense |
probably benign |
0.03 |
|
IGL01913:Pcdh18
|
APN |
3 |
49,709,698 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
IGL01915:Pcdh18
|
APN |
3 |
49,699,370 (GRCm39) |
missense |
probably benign |
|
|
IGL02095:Pcdh18
|
APN |
3 |
49,710,605 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL02128:Pcdh18
|
APN |
3 |
49,711,135 (GRCm39) |
missense |
possibly damaging |
0.65 |
|
IGL02302:Pcdh18
|
APN |
3 |
49,710,387 (GRCm39) |
missense |
probably benign |
|
|
IGL02342:Pcdh18
|
APN |
3 |
49,710,493 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02440:Pcdh18
|
APN |
3 |
49,699,052 (GRCm39) |
utr 3 prime |
probably benign |
|
|
IGL02499:Pcdh18
|
APN |
3 |
49,707,896 (GRCm39) |
missense |
probably benign |
0.15 |
|
IGL02570:Pcdh18
|
APN |
3 |
49,711,074 (GRCm39) |
missense |
probably benign |
0.02 |
|
IGL02745:Pcdh18
|
APN |
3 |
49,710,340 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03073:Pcdh18
|
APN |
3 |
49,707,816 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
PIT4469001:Pcdh18
|
UTSW |
3 |
49,709,518 (GRCm39) |
missense |
probably benign |
|
|
R0078:Pcdh18
|
UTSW |
3 |
49,710,793 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0196:Pcdh18
|
UTSW |
3 |
49,711,147 (GRCm39) |
splice site |
probably null |
|
|
R0524:Pcdh18
|
UTSW |
3 |
49,710,091 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R0661:Pcdh18
|
UTSW |
3 |
49,707,767 (GRCm39) |
missense |
possibly damaging |
0.64 |
|
R0900:Pcdh18
|
UTSW |
3 |
49,711,252 (GRCm39) |
missense |
probably benign |
0.25 |
|
R1101:Pcdh18
|
UTSW |
3 |
49,707,828 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1463:Pcdh18
|
UTSW |
3 |
49,709,854 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1778:Pcdh18
|
UTSW |
3 |
49,710,083 (GRCm39) |
missense |
probably benign |
0.19 |
|
R1850:Pcdh18
|
UTSW |
3 |
49,710,854 (GRCm39) |
missense |
probably benign |
0.22 |
|
R1875:Pcdh18
|
UTSW |
3 |
49,709,154 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1903:Pcdh18
|
UTSW |
3 |
49,709,896 (GRCm39) |
missense |
probably benign |
|
|
R1956:Pcdh18
|
UTSW |
3 |
49,710,400 (GRCm39) |
missense |
probably benign |
|
|
R2044:Pcdh18
|
UTSW |
3 |
49,709,389 (GRCm39) |
missense |
probably benign |
|
|
R2303:Pcdh18
|
UTSW |
3 |
49,709,723 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3732:Pcdh18
|
UTSW |
3 |
49,709,240 (GRCm39) |
missense |
probably benign |
|
|
R3732:Pcdh18
|
UTSW |
3 |
49,709,240 (GRCm39) |
missense |
probably benign |
|
|
R3733:Pcdh18
|
UTSW |
3 |
49,709,240 (GRCm39) |
missense |
probably benign |
|
|
R3973:Pcdh18
|
UTSW |
3 |
49,709,035 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4281:Pcdh18
|
UTSW |
3 |
49,710,982 (GRCm39) |
missense |
possibly damaging |
0.76 |
|
R4601:Pcdh18
|
UTSW |
3 |
49,699,174 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4631:Pcdh18
|
UTSW |
3 |
49,710,890 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R4752:Pcdh18
|
UTSW |
3 |
49,709,563 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4840:Pcdh18
|
UTSW |
3 |
49,699,117 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R4867:Pcdh18
|
UTSW |
3 |
49,709,113 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5039:Pcdh18
|
UTSW |
3 |
49,709,305 (GRCm39) |
missense |
probably benign |
|
|
R5169:Pcdh18
|
UTSW |
3 |
49,710,415 (GRCm39) |
missense |
possibly damaging |
0.65 |
|
R5438:Pcdh18
|
UTSW |
3 |
49,710,465 (GRCm39) |
nonsense |
probably null |
|
|
R5579:Pcdh18
|
UTSW |
3 |
49,699,426 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6000:Pcdh18
|
UTSW |
3 |
49,708,913 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6220:Pcdh18
|
UTSW |
3 |
49,699,700 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6737:Pcdh18
|
UTSW |
3 |
49,710,344 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R6789:Pcdh18
|
UTSW |
3 |
49,710,364 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7011:Pcdh18
|
UTSW |
3 |
49,709,231 (GRCm39) |
missense |
probably benign |
|
|
R7146:Pcdh18
|
UTSW |
3 |
49,710,271 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7150:Pcdh18
|
UTSW |
3 |
49,709,143 (GRCm39) |
missense |
probably benign |
0.31 |
|
R7205:Pcdh18
|
UTSW |
3 |
49,709,923 (GRCm39) |
missense |
probably benign |
|
|
R7326:Pcdh18
|
UTSW |
3 |
49,711,309 (GRCm39) |
missense |
probably benign |
|
|
R7413:Pcdh18
|
UTSW |
3 |
49,699,232 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R7755:Pcdh18
|
UTSW |
3 |
49,709,278 (GRCm39) |
missense |
possibly damaging |
0.59 |
|
R7848:Pcdh18
|
UTSW |
3 |
49,710,446 (GRCm39) |
missense |
possibly damaging |
0.54 |
|
R8169:Pcdh18
|
UTSW |
3 |
49,699,684 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8264:Pcdh18
|
UTSW |
3 |
49,711,030 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8352:Pcdh18
|
UTSW |
3 |
49,699,624 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
R8406:Pcdh18
|
UTSW |
3 |
49,710,998 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8452:Pcdh18
|
UTSW |
3 |
49,699,624 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
R8489:Pcdh18
|
UTSW |
3 |
49,709,038 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8526:Pcdh18
|
UTSW |
3 |
49,710,023 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9075:Pcdh18
|
UTSW |
3 |
49,699,339 (GRCm39) |
missense |
probably benign |
|
|
R9285:Pcdh18
|
UTSW |
3 |
49,707,786 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R9316:Pcdh18
|
UTSW |
3 |
49,709,089 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9339:Pcdh18
|
UTSW |
3 |
49,709,335 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9410:Pcdh18
|
UTSW |
3 |
49,699,615 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9425:Pcdh18
|
UTSW |
3 |
49,709,051 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
R9432:Pcdh18
|
UTSW |
3 |
49,699,667 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R9547:Pcdh18
|
UTSW |
3 |
49,709,506 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R9567:Pcdh18
|
UTSW |
3 |
49,710,884 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R9622:Pcdh18
|
UTSW |
3 |
49,711,229 (GRCm39) |
missense |
probably benign |
0.20 |
|
R9687:Pcdh18
|
UTSW |
3 |
49,711,036 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- TGTACTTGAGATAGGTCCACCC -3'
(R):5'- TCATCCTAAAAGGCCATCCAGG -3'
Sequencing Primer
(F):5'- AGTGGAACTGCCTACTGTCATC -3'
(R):5'- TCCAGGCAGATTCACAAAGG -3'
|
| Posted On |
2016-06-06 |
Incidental Mutation